Hybrid gradient delivery system and operation

ABSTRACT

A solvent delivery system for a liquid chromatography system may include a first gradient proportioning valve in fluidic communication with a first plurality of sources of solvent and producing therefrom a first low-pressure gradient stream. The solvent delivery system may further include a second gradient proportioning valve in direct fluidic communication with an inlet of the first gradient proportioning valve and with a second plurality of sources of solvent, the second gradient proportioning valve producing a second low-pressure gradient stream from the second plurality of sources of solvent, wherein one solvent source of the first plurality of sources of solvent used by the first gradient proportioning valve to produce the first low-pressure gradient stream comprises the second low-pressure gradient stream. The solvent delivery system may also include a first pump in direct fluidic communication with the first gradient proportioning valve to receive and pressurize the first low-pressure gradient stream.

RELATED APPLICATIONS

This application is a Continuation Application of and claims the benefitof and priority to co-pending U.S. patent application Ser. No.14/364,148 titled “Hybrid Gradient Delivery System and Operation,” whichis a U.S. National Stage Application claiming the benefit of andpriority to International Application No. PCT/US12/68520, filed Dec. 7,2012, titled “Hybrid Gradient Delivery System and Operation,” whichclaims the benefit of and priority to U.S. Provisional Application No.61/570,446, filed Dec. 14, 2011, titled “Hybrid Gradient Delivery Systemand Operation,” the entirety of each of these applications beingincorporated by reference herein.

FIELD OF THE INVENTION

The invention relates generally to liquid chromatography systems. Morespecifically, the invention relates to hybrid gradient delivery systemsthat combine aspects of high-pressure gradient systems and low-pressuregradient systems.

BACKGROUND

Chromatography is a set of techniques for separating a mixture into itsconstituents. In liquid chromatography systems, generally, one or morehigh-pressure pumps take in solvents and deliver a liquid solventcomposition to a sample manager, where a sample awaits injection intothe mixture. The sample is the material under analysis, examples ofwhich include complex mixtures of proteins, protein precursors, proteinfragments, reaction products, and other compounds, to list but a few.From the sample manager, the resulting liquid composition, comprised ofthe mixture of solvents and injected sample, moves to a point of use,such as a column of particulate matter. By passing the compositionthrough the column, the various constituents in the sample separate fromeach other at different rates and thus elute from the column atdifferent times. A detector receives the elution from the column andproduces an output from which the identity and quantity of the analytesmay be determined.

High-performance liquid chromatography (HPLC) uses two basic elutionmodes: isocratic elution and gradient elution. In the isocratic elutionmode, the mobile phase, comprised of either a pure solvent or a mixtureof solvents, remains the same throughout the chromatography run. In thegradient elution mode, the composition of the mobile phase changesduring the separation. Creation of the gradient (i.e., changing mobilephase composition) entails the mixing of multiple solvents, theproportions of which change over time in accordance with a predeterminedtimetable. Some HPLC systems create the gradient under high pressure, bymixing the solvents downstream of the pumps. Such HPLC systems are alsoreferred to herein as high-pressure gradient systems. Other HPLC systemscreate the gradient under low pressure, using a gradient proportioningvalve to select from up to four solvents, mixing the multiple solventsin front of a single aspirating pump, and changing the proportions ofthe solvents over time. Such HPLC systems are also referred to herein aslow-pressure gradient systems.

The decision between a high-pressure and a low-pressure gradient systeminvolves a variety of tradeoffs, only a few of which are mentioned here.For one, high-pressure gradient systems have lesser dwell volumes thanlow-pressure gradient systems because the solvent mixing occurs afterthe pumps instead of before the intake side of the pump. However,because of the location of mixing, low-pressure gradient systems canproduce a gradient with just one pump, whereas high-pressure gradientsystems generally require one pump for each solvent. Hence, low-pressuregradient systems are more amenable than high-pressure gradient systemsto tertiary and quaternary gradients, and are thus predominantly usedfor such chromatography applications, whereas high-pressure gradientsystems are generally used for binary gradients.

Often, however, it is desirable to blend more than two solvents in agradient, with a third solvent being a modifier, such as TFA(triflouroacetic acid), introduced at a constant percentage.Furthermore, it is easier to blend in a more concentrated mixture of themodifier to the total composition than to add the modifier to each ofthe other solvents at the desired lower concentration. For example, if0.1% TFA is the desired concentration, it is much easier to produce a 1%concentration of TFA, and introduce it in 10% proportion to the othertwo solvents, than to mix a 0.1% concentration of TFA in each of theother two solvents. Hence, a low-pressure gradient system is generallyused for chromatography runs to introduce the third modifier solventinstead of a high-pressure gradient system. Use of the low-pressuregradient system for this purpose, though, has disadvantages of anincreased dwell volume (in comparison to a high-pressure gradientsystem) and limiting the maximum percentage of one of the two othersolvents to 90%.

SUMMARY

In one aspect, the invention features a solvent delivery system for usein a liquid chromatography system. The solvent delivery system mayinclude a first gradient proportioning valve in fluidic communicationwith a first plurality of sources of solvent and producing therefrom afirst low-pressure gradient stream. The solvent delivery system may alsoinclude a second gradient proportioning valve in direct fluidiccommunication with an inlet of the first gradient proportioning valveand with a second plurality of sources of solvent, the second gradientproportioning valve producing a second low-pressure gradient stream fromthe second plurality of sources of solvent, wherein one solvent sourceof the first plurality of sources of solvent used by the first gradientproportioning valve to produce the first low-pressure gradient streamcomprises the second low-pressure gradient stream. The solvent deliverysystem may additionally include a first pump in direct fluidiccommunication with the first gradient proportioning valve to receive andpressurize the first low-pressure gradient stream and to move the firstpressurized low-pressure gradient stream to a flow-combining device.

In another aspect, the invention features a solvent delivery system foruse in a liquid chromatography system. The solvent delivery system mayinclude a first gradient proportioning valve in fluidic communicationwith a first plurality of sources of solvent and producing therefrom afirst low-pressure gradient stream. The solvent delivery system may alsoinclude a first pump in direct fluidic communication with the firstgradient proportioning valve to receive and pressurize the firstlow-pressure gradient stream and to move the first pressurizedlow-pressure gradient stream to a flow-combining device. The solventdelivery system may further include a second gradient proportioningvalve in fluidic communication with a second plurality of sources ofsolvent, the second gradient proportioning valve producing a secondlow-pressure gradient stream from the second plurality of sources ofsolvent. The solvent delivery system may additionally include a secondpump operating in parallel with the first pump and in direct fluidiccommunication with an outlet of the second gradient proportioning valveto receive and pressurize the second low-pressure gradient stream and tomove the second pressurized low-pressure gradient stream to theflow-combining device where the pressurized solvent stream combines withthe first pressurized low-pressure gradient stream to produce ahigh-pressure gradient stream.

In still another aspect, the invention features a solvent deliverysystem for use in a liquid chromatography system. The solvent deliverysystem may include a first gradient proportioning valve in fluidiccommunication with a first plurality of sources of solvent and producingtherefrom a first low-pressure gradient stream. The solvent deliverysystem may also include a first pump in direct fluidic communicationwith an outlet of the first gradient proportioning valve to receive andpressurize the first low-pressure gradient stream and to move the firstpressurized low-pressure gradient stream to a flow-combining device. Thesolvent delivery system may further include a second pump operating inparallel with the first pump, the second pump moving a pressurizedsolvent stream to the flow-combining device where the pressurizedsolvent stream combines with the first pressurized low-pressure gradientstream to produce a high-pressure gradient stream.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and further advantages of this invention may be betterunderstood by referring to the following description in conjunction withthe accompanying drawings, in which like numerals indicate likestructural elements and features in various figures. The drawings arenot necessarily to scale, emphasis instead being placed uponillustrating the principles of the invention.

FIG. 1 is a functional block diagram of an embodiment of a hybridsolvent delivery system for a liquid chromatography system, the hybridsolvent delivery system combining features of a high-pressure gradientsystem and a low-pressure gradient system.

FIG. 2 is a functional block diagram of another embodiment of a hybridsolvent delivery system.

FIG. 3 is a functional block diagram of another embodiment of a hybridsolvent delivery system.

DETAILED DESCRIPTION

Solvent delivery systems described herein can be deemed hybrid systemsbecause they combine features of a high-pressure gradient system withthose of a low-pressure gradient system. As a hybrid, the solventdelivery systems function primarily as binary gradient systems havingminimized dwell volume and flexibility for solvent selection.

FIG. 1 shows an embodiment of a hybrid solvent delivery system 10 forproducing and moving a solvent composition to a sample manager (notshown), also known as an autosampler, where a sample is introduced tothe solvent composition. The features of a high-pressure gradient systemadapted for use by the hybrid solvent delivery system 10, outlined bydashed box 16, include two pumps 14-1, 14-2 (generally, 14) operating inparallel. In brief overview, each pump 14-1, 14-2 includes a primarypumping actuator and an accumulator pumping actuator coupled in series.The pumps 14 can be of the type used in the 2545 Binary Gradient Modulemanufactured by Waters Corporation of Milford, Mass.

The outlets of the pump 14-1, 14-2 are connected at the same orsubstantially the same mechanical location, here represented as aflow-combining device (FCD) 20. Example implementations of theflow-combining device 20 include, but are not limited to, a T-sectionand a mixer. Each pump 14-1, 14-2 moves a solvent stream 18-1, 18-2,respectively, at high pressure, to this flow-combining device 20, wherethe pressurized solvent streams 18-1, 18-2 combine to produce apressurized solvent composition 22 that is delivered over time to thesample manager. A gradient controller 24 is in communication with thepumps 14 to manage the speed of each pump 14 in order to deliver more orless of each solvent stream 18-1, 18-2 over the course of theseparation.

The features of the hybrid solvent delivery system 10 adapted from alow-pressure gradient system are shown within dashed box 26 and includetwo gradient proportioning valves (GPV) 28-1, 28-2 (generally, 28)operating in parallel. Each GPV 28 is in fluidic communication with upto four solvent reservoirs 30 (here, only two reservoirs per GPV areshown; the GPV 28-1 is in fluidic communication with solvent reservoirs30-1, 30-2; and the GPV 28-2 is in fluidic communication with solventreservoirs 30-3, 30-4). In addition, each GPV 28 is in fluidiccommunication with one of the pumps 14; the pump 14-1 acquires thelow-pressure gradient stream 32-1 from the GPV 28-1, and the pump 14-2acquires the low-pressure gradient stream 32-2 from GPV 28-2.

Each GPV 28 includes an inlet for each reservoir 30, an inlet valve (notshown) for controlling each flow of fluid being drawn into one of theinlets, and a common outlet through which fluid flows from the GPV 28 toone of the pumps 14. A conduit for transporting fluid, for example, atube, extends from each reservoir 30 to one of the inlets of the GPV 28and from the outlet of the GPV 28 to the intake side of the pump 14. Anexample implementation of a gradient proportioning valve is described inU.S. Pat. No. 5,862,832, issued Jan. 26, 1999, the entirety of whichpatent is incorporated by reference herein.

The gradient controller 24 is in communication with the GPVs 28 toactuate their individual valves sequentially at the appropriate times,thereby managing the intake of fluid from the reservoirs 30 for mixingin desired proportions and producing low-pressure gradient streams 32over time. From solvent reservoirs 30-1, 30-2, the GPV 28-1 produceslow-pressure gradient stream 32-1, and from solvent reservoirs 30-3,30-4, the GPV 28-2 produces low-pressure gradient stream 32-2. Thesegradient streams 32 are produced ahead of the pumps 14, and thus underlow pressure.

During operation, the pump 14-1 draws and pressurizes the low-pressuregradient stream 32-1 produced by the GPV 28-1, and moves the resultingpressurized low-pressure gradient stream 18-1 to the flow-combiningdevice 20, while the pump 14-2 draws and pressurizes the low-pressuregradient stream 32-2 produced by the GPV 28-2, and moves the resultingpressurized low-pressure gradient stream 18-2 to the flow-combiningdevice 20, where the two pressurized low-pressure gradient streams 18-1,18-2 combine to produce the pressurized solvent stream 22. Because theflow-combining device 20 is downstream of the pumps 14 the solventstream 22 is produced at high pressure (e.g., in the range between5000-15000 psi). As used herein, the phrase “pressurized low-pressuregradient stream” refers to a low-pressure gradient stream that isproduced by a GPV and subsequently pressurized to a high pressure by apump 14.

As an illustration of the operation, consider for example that solventreservoir 30-1 contains water, solvent reservoir 30-2 contains 1% TFA inwater, solvent reservoir 30-3 contains solvent B, and solvent reservoir30-4 contains 1% TFA in solvent B. To achieve a solvent composition with0.1% TFA modifier, the gradient controller 24 can control the GPV 28-1to take a 90% proportion of solvent reservoir 30-1 (water) and a 10%proportion of solvent reservoir 30-2 (1% TFA in water) to produce alow-pressure gradient stream 32-1 of 0.1% TFA in water. In addition, thegradient controller 24 can control the GPV 28-2 to take a 90% proportionof solvent reservoir 30-3 (solvent B) and a 10% proportion of solventreservoir 30-4 (1% TFA in solvent B) to produce a low-pressure gradientstream 32-2 of 0.1% TFA in solvent B. The pumps 14 draw and pressurizethe low-pressure gradient streams 32-1, 32-2, and combine the resultingpressurized low-pressure gradient streams 18-1, 18-2 to produce apressurized solvent stream 22 comprised of water, solvent B, and 0.1%TFA. The maximum achievable proportion of solvent B is 100%.

In an alternative embodiment, the hybrid solvent delivery system canhave one GPV 28 only. For example, consider that GPV 28-2 and thesolvents 30-3, 30-4 are not part of the hybrid solvent delivery system10 shown in FIG. 1, and that the pump 14-2 is instead in direct fluidiccommunication with a solvent reservoir 30-5. During operation of thisembodiment, the pump 14-1 draws and pressurizes the low-pressuregradient stream 32-1 produced by the GPV 28-1, and moves the resultingpressurized low-pressure gradient stream 32-1 to the flow-combiningdevice 20, while the pump 14-2 draws, pressurizes, and moves solventfrom reservoir 30-5 to the flow-combining device 20, where thepressurized low-pressure gradient stream 18-1 combines with the solvent30-5. If the pump 14-2 is turned off, any of the embodiments of thehybrid solvent delivery system 10 can be adapted to operate like aconventional low-pressure gradient system.

FIG. 2 shows another embodiment of a hybrid solvent delivery system 50,which adds a second stage of GPVs 52 to the hybrid solvent deliverysystem 10 of FIG. 1. More specifically, the hybrid solvent deliverysystem 50 includes a GPV 52-1 in fluidic communication with a pluralityof solvent reservoirs 54-1, 54-2 and a GPV 52-2 in fluidic communicationwith a plurality of solvent reservoirs 54-3, 54-4. The outlet of GPV52-1 is in fluidic communication with one of the inlets of GPV 28-1,while the outlet of GPV 52-2 is in fluidic communication with one of theinlets of GPV 28-2. The gradient controller 24 is in communication withthe GPVs 52 to manage the intake of fluid from the reservoirs 54 formixing in desired proportions and producing low-pressure gradientstreams 56-1, 56-2 (generally, 56) over time. From solvent reservoirs54-1, 54-2, the GPV 52-1 produces low-pressure gradient stream 56-1, andfrom solvent reservoirs 54-3, 54-4, the GPV 52-2 produces low-pressuregradient stream 56-2.

During operation, the low-pressure gradient stream 32-1 produced by theGPV 28-1 includes a proportion of the low-pressure gradient stream 56-1produced by the GPV 52-1. The pump 14-1 draws and pressurizes thelow-pressure gradient stream 32-1, and moves the resulting pressurizedlow-pressure gradient stream 18-1 to the flow-combining device 20.Concurrently, the GPV 28-2 produces the low-pressure gradient stream32-2, which includes a proportion of the low-pressure gradient stream56-2 produced by the GPV 56-2. The pump 14-2 draws and pressurizes thelow-pressure gradient stream 32-2, and moves the resulting pressurizedlow-pressure gradient stream 18-2 to the flow-combining device 20, wherethe two pressurized low-pressure gradient streams 18-1, 18-2 combine toproduce the pressurized solvent stream 22. In one embodiment, thegradient controller 24 centrally controls the various compositions ofeach low-pressure gradient stream 32, 56 and the resulting high-pressuregradient stream (i.e., solvent stream 22). In other embodiments, thegradient controller 24 includes a plurality of decentralized controllersthat intercommunicate and manage the various compositions in fashion.

In alternative embodiments, the hybrid solvent delivery system 50 canhave one second-stage GPV 52 only or one second-stage GPV 52 and onefirst-stage GPV 28. For example, for one alternative the GPV 52-2 andthe solvents 54-3, 54-4 are not part of the hybrid solvent deliverysystem 50 shown in FIG. 2; in another example alternative, both the GPV52-2 and GPV 28-2 are not part of the hybrid solvent delivery system 50.Again, if the pump 14-2 is turned off, any of the embodiments of thehybrid solvent delivery system 50 can be adapted to operate like aconventional low-pressure gradient system.

FIG. 3 shows another embodiment of a hybrid solvent delivery system 60,which fluidically connects a switch valve 62 to one of the GPVs 28 ofthe hybrid solvent delivery system 10 of FIG. 1. More specifically, thehybrid solvent delivery system 60 includes a switch valve 62 in fluidiccommunication with a plurality of solvent bottles (or reservoirs) 64-1,64-2, 64-3, 64-4, 64-5, and 64-6. In this example, the outlet of theswitch valve 62 is in fluidic communication with one of the inlets ofthe GPV 28-2. The gradient controller 24 is in communication with theswitch valve 62 to select one of the inlets of the switch valve 62, and,thus, the particular solvent bottle 64 from which to draw solvent.

From the solvent drawn through the switch valve 62 and from solventreservoirs 30-3, 30-4, the GPV 28-2 produces the low-pressure gradientstream 32-2. The pump 14-1 draws and pressurizes the low-pressuregradient stream 32-1 produced by the GPV 28-1 and moves the resultingpressurized low-pressure gradient stream 18-1 to the flow-combiningdevice 20, while the pump 14-2 draws and pressurizes the low-pressuregradient stream 32-2, and moves the resulting pressurized low-pressuregradient stream 18-2, which includes the solvent from the selectedsolvent bottle 64, to the flow-combining device 20, where thepressurized low-pressure gradient streams 18-1, 18-2 combine.

In like fashion, another switch valve and set of solvent bottles can befluidically connected to an inlet of the GPV 28-1 instead of or incombination with the switch valve 62 and solvent bottles 64 connected tothe GPV 28-2. The embodiments of FIG. 3 are merely illustrative examplesof the varying complexity that can be built into a hybrid solventdelivery system.

While the invention has been shown and described with reference tospecific preferred embodiments, it should be understood by those skilledin the art that various changes in form and detail may be made thereinwithout departing from the spirit and scope of the invention as definedby the following claims.

What is claimed is:
 1. A solvent delivery system for use in a liquidchromatography system, comprising: a first gradient proportioning valvein fluidic communication with a first plurality of sources of solventand producing therefrom a first low-pressure gradient stream; a secondgradient proportioning valve in direct fluidic communication with aninlet of the first gradient proportioning valve and with a secondplurality of sources of solvent, the second gradient proportioning valveproducing a second low-pressure gradient stream from the secondplurality of sources of solvent, wherein one solvent source of the firstplurality of sources of solvent used by the first gradient proportioningvalve to produce the first low-pressure gradient stream comprises thesecond low-pressure gradient stream; and a first pump in direct fluidiccommunication with the first gradient proportioning valve to receive andpressurize the first low-pressure gradient stream and to move the firstpressurized low-pressure gradient stream to a flow-combining device. 2.The solvent delivery system of claim 1, further comprising: a secondpump operating in parallel with the first pump, the second pump moving apressurized solvent stream to the flow-combining device where thepressurized solvent stream combines with the first pressurizedlow-pressure gradient stream to produce a high-pressure gradient stream.3. The solvent delivery system of claim 2, further comprising: acontroller in communication with the first pump, the second pump, andthe first gradient proportioning valve, the controller centrallycontrolling operation of the first pump and the first gradientproportioning valve at appropriate times to determine a composition ofthe first low-pressure gradient stream and a composition of thehigh-pressure gradient stream over time.
 4. The solvent delivery systemof claim 1, wherein the first gradient proportioning valve is in directfluidic communication with a first plurality of solvent reservoirs. 5.The solvent delivery system of claim 4, wherein the first gradientproportioning valve includes an inlet for each of the first plurality ofsolvent reservoirs.
 6. The solvent delivery system of claim 5, whereinthe first gradient proportioning valve includes an inlet valve forcontrolling flow of fluid being drawn into one of the inlets for thefirst plurality of solvent reservoirs.
 7. The solvent delivery system ofclaim 1, wherein the first gradient proportioning valve includes acommon outlet through which fluid flows from the first gradientproportioning valve to the first pump.
 8. A solvent delivery system foruse in a liquid chromatography system, comprising: a first gradientproportioning valve in fluidic communication with a first plurality ofsources of solvent and producing therefrom a first low-pressure gradientstream; a first pump in direct fluidic communication with the firstgradient proportioning valve to receive and pressurize the firstlow-pressure gradient stream and to move the first pressurizedlow-pressure gradient stream to a flow-combining device; a secondgradient proportioning valve in fluidic communication with a secondplurality of sources of solvent, the second gradient proportioning valveproducing a second low-pressure gradient stream from the secondplurality of sources of solvent; and a second pump operating in parallelwith the first pump and in direct fluidic communication with an outletof the second gradient proportioning valve to receive and pressurize thesecond low-pressure gradient stream and to move the second pressurizedlow-pressure gradient stream to the flow-combining device where thepressurized solvent stream combines with the first pressurizedlow-pressure gradient stream to produce a high-pressure gradient stream.9. The solvent delivery system of claim 8, further comprising: acontroller in communication with the first pump, the second pump, andthe first gradient proportioning valve, the controller centrallycontrolling operation of the first pump and the first gradientproportioning valve at appropriate times to determine a composition ofthe first low-pressure gradient stream and a composition of thehigh-pressure gradient stream over time.
 10. The solvent delivery systemof claim 8, further comprising: a first switch valve in fluidiccommunication with the first gradient proportioning valve and with athird plurality of sources of solvent, the first switch valve beingconfigured to provide a fluidic path for a selected source of the thirdplurality of sources of solvent, wherein one of the sources of the firstplurality of sources of solvent used by the first gradient proportioningvalve to produce the low-pressure gradient stream comprises the selectedsource of the third plurality of sources of solvent.
 11. The solventdelivery system of claim 10, further comprising: a second switch valvein fluidic communication with the second gradient proportioning valveand with a fourth plurality of sources of solvent, the second switchvalve being configured to provide a fluidic path for a selected sourceof the fourth plurality of sources of solvent, wherein one of thesources of the second plurality of sources of solvent used by the secondgradient proportioning valve to produce the low-pressure gradient streamcomprises the selected source of the fourth plurality of sources ofsolvent.
 12. The solvent delivery system of claim 8, wherein the firstgradient proportioning valve is in direct fluidic communication with afirst plurality of solvent reservoirs.
 13. The solvent delivery systemof claim 12, wherein the first gradient proportioning valve includes aninlet for each of the first plurality of solvent reservoirs.
 14. Thesolvent delivery system of claim 13, wherein the first gradientproportioning valve includes an inlet valve for controlling flow offluid being drawn into one of the inlets for the first plurality ofsolvent reservoirs.
 15. The solvent delivery system of claim 8, whereinthe first gradient proportioning valve includes a common outlet throughwhich fluid flows from the first gradient proportioning valve to thefirst pump.
 16. A solvent delivery system for use in a liquidchromatography system, comprising: a first gradient proportioning valvein fluidic communication with a first plurality of sources of solventand producing therefrom a first low-pressure gradient stream; a firstpump in direct fluidic communication with an outlet of the firstgradient proportioning valve to receive and pressurize the firstlow-pressure gradient stream and to move the first pressurizedlow-pressure gradient stream to a flow-combining device; and a secondpump operating in parallel with the first pump, the second pump moving apressurized solvent stream to the flow-combining device where thepressurized solvent stream combines with the first pressurizedlow-pressure gradient stream to produce a high-pressure gradient stream.17. The solvent delivery system of claim 16, wherein the second pump isin direct fluidic communication with a solvent reservoir.
 18. Thesolvent delivery system of claim 16, further comprising: a controller incommunication with the first pump, the second pump, and the firstgradient proportioning valve, the controller centrally controllingoperation of the first pump and the first gradient proportioning valveat appropriate times to determine a composition of the firstlow-pressure gradient stream and a composition of the high-pressuregradient stream over time.
 19. The solvent delivery system of claim 16,wherein the first gradient proportioning valve is in direct fluidiccommunication with a first plurality of solvent reservoirs.
 20. Thesolvent delivery system of claim 4, wherein the first gradientproportioning valve includes an inlet for each of the first plurality ofsolvent reservoirs.